Glucocorticoid Receptor-Mediated Induction of Glutamine Synthetase in Skeletal Muscle Cellsin Vitro*

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Abstract
We studied the regulation by glucocorticoids of glutamine synthetase in L6 mouse cells in culture. Glutamine synthetase activity was strikingly enhanced by dexamethasone. The dexamethasone-mediated induction of glutamine synthetase activity was blocked by RU38486 [11.beta.-(4-dimethylaminophenyl)17.beta.-hydroxy-17.alpha.-(prop-1-ynyl)estra-4,9-dien-3-one], a glucocorticoid receptors in the induction process. RU38486 alone was without effect. Northern blot analysis revealed that dexamethasone-mediated enhancement of glutamine synthetase activity involves increased levels of glutamine synthetase mRNA. Increased enzyme activity was specific for glucocorticoids; other steroid hormones were essentially without effect. The induction of glutamine synthetase was selective, in that glutaminase activity was not induced by dexamethasone treatment of L6 cells. Thus, glucocorticoids regulate the expression of glutamine synthetase mRNA in cultured muscle cells via interaction with intracellular receptors. Such regulation may be relevant to control of glutamine production by muscle.